Dead Cows, and a Bull Run?

One hundred and fifty one years ago, Charles Darwin and Alfred Russel Wallace knew that birds dropping from the skies, dead fish and crabs washing up from the sea, and cows flopping in the fields, are nature’s spectacular staging of what Darwin termed natural selection. Darwin wrote, “As many more individuals of each species are born than can possibly survive; and as, consequently, there is a frequently recurring struggle for existence, it follows that any being, if it vary however slightly in any manner profitable to itself, under the complex and sometimes varying conditions of life, will have a better chance of surviving, and thus be naturally selected. From the strong principle of inheritance, any selected variety will tend to propagate its new and modified form.”

“It may metaphorically be said,” Darwin wrote, “that natural selection is daily and hourly scrutinizing, throughout the world, the slightest variations; rejecting those that are bad, preserving and adding up all that are good; silently and insensibly working, whenever and wherever opportunity offers….We see nothing of these slow changes in progress, until the hand of time has marked the lapse of ages, and then so imperfect is our view into long-past geological ages, that we see only that the forms of life are now different from what they formerly were.”

Wallace wrote, “An antelope with shorter or weaker legs must necessarily suffer more from the attacks of the feline carnivora; the passenger pigeon with less powerful wings would sooner or later be affected in its powers of procuring a regular supply of food . . . If, on the other hand, any species should produce a variety having slightly increased powers of preserving existence, that variety must inevitably in time acquire a superiority in numbers. . . . Now, let some alteration of physical conditions occur in the district – a long period of drought, a destruction of vegetation by locusts, the irruption of some new carnivorous animal seeking “pastures new” . . . it is evident that, of all the individuals composing the species, those forming the least numerous and most feebly organized variety would suffer first, and, were the pressure severe, must soon become extinct.”

In experiments conducted in the department of obstetrics at the Columbia Medical School in the 1920’s, Raphael Kurzrock and Charles Lieb noticed that when they attempted artificial insemination the uterus often expelled the semen. They found that human seminal fluid could affect the state of contraction of strips of muscle from the uterus, either contracting or relaxing them. They remarked in a paper published in 1930 that the history of the patients from whom the muscle strips were obtained made their experiments even more intriguing. Muscle from patients with a history of successful pregnancy responded to semen by relaxing, while semen always induced contractions in uterine muscle from women with a history of long acting sterility. This suggested to Kurzrock and Lieb the presence of factors in semen and uteri that differentiate between infertility and fertility. After studying this paper on numerous occasions, I realized that these factors are also those of natural selection.

In the early 1930’s, Maurice Goldblatt in the United States and Ulf von Euler in Sweden showed that factors in the seminal fluid of boars act on various smooth muscles and lower blood pressure. Von Euler named these substances “prostaglandins” because the prostate contains small amounts of them, and he assumed that what he had extracted from semen must have come from that gland. Today we know that every cell manufactures prostaglandins, or other members of the eicosanoid family. Prostaglandins are ephemeral, infinitesimal, and powerful molecules that signal throughout each cell, from cell to cell, organ to organ, brain to body, and body to brain. They are not produced under resting conditions, but only in response to stimuli. If the enzymes that produce and degrade prostaglandins are resilient, they can absorb stress and continue to function physiologically; if not, physiology becomes pathology.

At the Karolinska Institute in Stockholm, Sune Bergstrom purified several prostaglandins, determined their chemical structure, and showed that they are formed from essential fatty acids. After collaborating with Bergstrom from 1959-1962 on the structure of prostaglandins, Bengt Samuelsson provided a detailed picture of arachidonic acid and prostaglandin metabolism, and defined the chemical processes involved in their synthesis and breakdown. Samuelsson showed that platelets convert arachidonic acid to thromboxanes (TX’s), while white blood cells convert it to leukotrienes (LT’s). Thromboxanes constrict blood vessels and cause platelets to clump together and release more clotting factors. This is useful when clotting is necessary to stop bleeding; when this mechanism is overactive, it plays a pivotal role in heart attacks and strokes. And thromboxanes directly stimulate the smooth muscles of blood vessels to contract, including those of the heart and brain.

At Oxford University in the mid-sixties, Sir John Vane and his colleagues developed the cascade superfusion bioassay technique for measurement of the release and fate of vasoactive hormones in the circulation or in the perfusion fluid of isolated organs. In 1971 Vane made the fundamental discovery that anti-inflammatory compounds such as aspirin block the formation of prostaglandins and thromboxanes. Later Vane and Salvador Moncada isolated a prostaglandin in the wall of blood vessels and named it prostacyclin (PGI2). In dilating blood vessels and inhibiting the aggregation of platelets, prostacyclin opposes the actions of thromboxanes. In some countries patients with such vasoconstrictive disorders as Raynaud’s disease, peripheral vascular disease and pulmonary hypertension, whether spontaneous or caused by certain appetite suppressants, are treated with infusions of synthetic prostacyclin. For their pioneering research on prostaglandins, Bergstrom, Samuelson and Vane were awarded the Nobel Prize in Medicine in 1982.

In Arkansas, thousands of red-winged blackbirds dropped dead out of the sky. 100,000 drum fish died in the Arkansas River, birds in Louisiana and Kentucky. Pundits allowed that the birds died of blunt trauma to their organs and blood clots, resulting from a midair collision instigated by the sound of fireworks. Devil crabs, sardines, croaker, catfish, bream, carp, roach fish, starlings, Cowbirds, and jackdaw crows perished in their hundreds, thousands or millions. More than two hundred cows dropped dead in a field in Wisconsin. The blackbirds showed no signs of trauma or infection, but did have evidence of bleeding and clotting, indicating that thromboxane synthase, the enzyme that synthesizes thromboxane B2, was induced by environmental stress, the enzyme a variant Darwin and Wallace had in mind. .In the other sudden deaths, induction of an enzyme in the prostaglandin pathway were probably responsible. Emil Zuckerkandl and Linus Pauling advanced the idea that enzymes, they referred to a semantides, fulfill the functions of biological clocks, changing slowly over time

Could this tragic fate befall humans? It has, often, in the form of epidemics and pandemics. Individuals whose prostaglandin E2 production resisted viruses’ attempts to increase it survived, those unable to resist perished. Increased synthesis of prostaglandin E2 causes both depression and defective immune function, and depressives constitute a substantial segment of society. At the moment, a retrovirus, a variant of a virus, has taken thirty million lives. A glycoprotein in the envelop of HIV, stimulates the enzyme converting arachidonic acid to prostaglandin E2, well beyond other viruses, prostaglandin E2 the most powerful endogenous immunosuppressant known,. Natural selection differentiates between reproduction and sterility, survival and extinction.

Of the altered physical condition responsible for the mass deaths, rapid movement of the Magnetic North Pole towards Russia has the edge.